Prognostic value of liver fibrosis biomarkers: a meta-analysis

Abstract

Aims and methods: Several serum biomarkers such as FibroTest, aspartate transaminase-platelet ratio index (APRI), FIB-4, and liver stiffness measurement by FibroScan have been validated as alternatives to biopsy for the diagnosis of fibrosis in patients with chronic liver disease. This paper aims to assess the 5-year prognostic values of these biomarkers. A meta-analysis combined all published prognostic studies. Baseline biopsy and APRI data were used as references.

Results: Only 3 biomarkers had several prognostic validations: FibroTest (4 studies; 2,396 patients), APRI (5 studies; 2,422 patients), and FIB-4 (3 studies; 1,184 patients). For the prediction of survival without liver-related death, the areas under the receiver operating characteristic curves (AUROCs) were 0.86 for biopsy (95% confidence interval [CI], 0.77-0.95), 0.88 for FibroTest (95% CI, 0.79-0.98), 0.73 for FIB-4 (95% CI, 0.62-0.85), and 0.66 for APRI (95% CI, 0.57-0.75). APRI had a significantly lower prognostic value versus biopsy, with a mean difference between AUROCs of -0.21 (95% CI, -0.33 to -0.10; P<.001); FIB-4 had a significantly lower prognostic value versus biopsy, with a mean difference between AUROCs of -0.21 (95% CI, -0.20 to -0.02; P=.02). Only FibroTest did not show a significant difference in prognostic value versus biopsy, with a mean difference in AUROCs of +0.02 (95% CI, -0.05 to +0.09; P=.85).

Conclusion: FibroTest is a validated biomarker for the prognosis of patients with chronic liver disease.

Keywords: FIB-4; FibroScan; FibroTest; Fibrosis biomarkers; HepaScore; aspartate transaminase-platelet ratio index; biopsy; elastography; meta-analysis; prognostic value.

Figure 1

Meta-analysis of the prognostic value of fibrosis biomarkers versus random for survival without liver-related deaths (A). Meta-analysis of the prognostic value of fibrosis biomarkers versus random for overall survival (B). The horizontal lines indicate the 95% confidence interval for the mean difference between biomarkers and random (0.500) or between biomarkers' area under the receiver operating characteristic curves (AUROCs) and biopsy's AUROCs. The vertical lines indicate the equivalence line (0% difference). Positive differences indicate a difference in favor of the reference test (biopsy or aspartate transaminase-platelet ratio index [APRI] or FIB-4 or FibroTest or Other). When the horizontal line crosses the vertical line, there is no significant difference. *HepaScore; †FibroMeter.

Figure 2

Meta-analysis of the prognostic value of fibrosis biomarkers versus biopsy for survival without liver-related deaths (A). Meta-analysis of the prognostic value of fibrosis biomarkers versus biopsy for overall survival (B). The horizontal lines indicate the 95% confidence interval for the mean difference between biomarkers and random (0.500) or between biomarkers' area under the receiver operating characteristic curves (AUROCs) and biopsy's AUROCs. The vertical lines indicate the equivalence line (0% difference). Negative differences indicate a difference in favor of the reference test (biopsy). When the horizontal line crosses the vertical line, there is no significant difference. APRI=aspartate transaminase–platelet ratio index.

Figure 3

Meta-analysis of the prognostic value of FibroTest and FIB-4 versus aspartate transaminase-platelet ratio index (APRI) for survival without liver-related deaths (A). Meta-analysis of the prognostic value of FibroTest and FIB-4 versus APRI for overall survival (B). The horizontal lines indicate the 95% confidence interval for the mean difference between the area under the receiver operating characteristic curves (AUROCs) of the biomarkers (FIB-4 and FibroTest) and APRI. The vertical lines indicate the equivalence line (0% difference). Positive differences indicate a difference in favor of FibroTest. When the horizontal line crosses the vertical line, there is no significant difference (FIB-4).